The present invention relates to processes for preparing acetylenic active agents, useful in compositions for monitoring and providing a cumulative indication of exposure to certain deleterious ambient conditions. The invention also relates to systems, elements, components, and compositions incorporating such acetylenic agents and to indicators and other devices in which such compositions may be incorporated.
In particular, but without limitation, the invention relates to such compositions and the like which are useful for monitoring conditions to which an associated host product, for example, a foodstuff, a vaccine or a medication, has been exposed, including the elapse of a predetermined integral of deleterious ambient conditions which can correlate with the shelf life of such a product especially an integral of temperature over time. Such time-temperature indicators are referenced “TTI” herein. The elapse of a predetermined parameter or combination of parameters, for example time and temperature, can be indicated by a change in color or other visual characteristic.
Acetylenic agents including substituted diacetylenics and others are well known for use in shelf life monitoring systems. In general, as described in, for example, Patel et al. U.S. Pat. No. 3,999,946, acetylenic agents useful in the invention comprise polyacetylenic compounds having two or more conjugated acetylenic groups (—C≡C—C≡C—). These reactive groups cause the acetylenic active agents to polymerize, providing a distinct visual change, under many commonly encountered conditions of time and temperature and other environmental parameters. As taught by Patel et al. '946, useful acetylenic compounds may be monomeric or polymeric, cyclic or acyclic, provided that they contain at least two conjugated acetylenic groups. Examples of suitable acetylenic compounds include diynes, triynes, tetraynes and hexaynes. Patel et al. '946 disclose the synthesis of many diacetylenic monomers and other useful diacetylenic agents and their incorporation into TTIs and other shelf life indicator compositions where they may provide a cumulative indication of temperature fluctuations over time. Individual acetylenic agents may be selected, or tailored to specific applications, with varying degrees of difficulty to provide active agents with particular desired time-temperature or other condition-indicating characteristics. Such diacetylenic compounds and agents are generally suitable for the purposes of the present invention and are referenced herein as “acetylenic agents”.
Acetylenic agents useful for the purposes of the invention are sometimes described in the art, with more or less precision, as “monomers”, “diacetylenic monomers”, or “substituted diacetylenic monomers”. All such diacetylenic materials that can provide a detectable indication of exposure to an environmental condition, optionally on a cumulative basis, are to be understood to be embraced by the term “diacetylenic agent” as it us used herein.
Patel U.S. Pat. Nos. 4,189,399 and 4,384,980 and Preziosi et al. U.S. Pat. Nos. 4,789,637 and 4,788,151 provide examples of other acetylenic agents useful in shelf life systems, including modifications of such agents, broad ranges of substituents that may be made and complexes in which they may be incorporated, as well as methods of synthesis and blending, for example in co-crystallization operations that are known to the art and which may be employed in the practice of the present invention. The disclosure of each one of the aforementioned Patel and Preziosi patents is hereby incorporated herein by this specific reference thereto.
Condition-indicating acetylenic agents such as those described above have physico-chemical properties that are particularly useful for the purposes of the invention, for example an ability to polymerize in response to persistent temperature excursions and to transform into colored solid state reaction products which contrast strikingly with the starting material. Conditions monitored may include time, temperature, humidity, actinic radiation, vaporous atmosphere, and the like, to which an associated host product, for example a foodstuff, vaccine or medicament, or host organism, has been exposed, as well as combinations of two or more of the foregoing conditions.
Generally, acetylenic agents useful in the practice of the invention can give a distinct visual indication, such as a change of color hue or of color density, of the elapse of a predetermined time-temperature integral which may be selected to flag the expiration of the shelf life of the associated host product.
Conveniently the acetylenic agent may be embodied in a product label affixed to a perishable or freshness-sensitive host product, for example a foodstuff or a medicament or the like, which product is known to be adversely affected by, for example, excessive thermal exposure.
Usefully, especially for inclusion as an element of a product label, the acetylenic agent is incorporated into a composition formulated as a printable ink. The resultant printable ink may be applied in a suitable pattern to a label, wrapper or wrapping component, which can be associated, by adhesive layer or other means, with a target product having a limited shelf life, for example, an item of foodstuff or medicament. Desirably, at the expiration of a predetermined period, the applied TTI ink label composition displays a predesignated color or color density, signaling expiration of the product's shelf life. A reference mark may be provided closely adjacent to the TTI to facilitate visual determination of the predesignated color or color density.
It should be noted that although the term “monomer” is sometimes used to denote active acetylenic monitor component materials intended to be employed in TTIs, dimeric and polymeric component compounds derived from a similar basic structure, for example as described in the above-mentioned references, can also be employed. The term “acetylenic agent” as used herein is intended to embrace various such reactive diacetylenic compounds that are capable of polymerizing in response to conditions of interest while providing a useful detectable parameter change, notably, but not exclusively, a distinct visual change. Other parameters, for example electrical parameters such as conductivity dielectric constant, or the like might be detected, if desired, and the invention can also employ reactive acetylenic agents capable of providing such other changes in response to relevant parameter changes.
As is known from the above-referenced patents, and other documents, numerous diacetylenic monomers and other useful acetylenic agents may be synthesized to yield TTI components of widely varying reactive temperature ranges and resultant color densities. Such acetylenic agents have long been employed to provide useful, reproducible results as indicators of shelf life end points, with largely satisfactory results.
Of considerable significance with regard to the above-described TTI technology is that, once the acetylenic agents have been synthesized and recovered, it is usually desirable to store them at relatively low temperatures, for example, below about 4° C. to inhibit premature polymerization. Also, further downstream processing operations, including application to a host product, are desirably performed at low temperature. Furthermore, even with careful storage, active acetylenic agents have relatively short shelf lives, as compared with other industrial fine chemicals normally stored at room temperature. The need for low-temperature storage impacts most aspects of the subsequent handling, processing and marketing of condition-indicating acetylenic agents and products incorporating them.
Generally, the acetylenic agents once synthesized are recovered in the solid state by precipitation as crystals from solution. For many purposes it is desirable that crystallization be performed rapidly to yield relatively small crystals or other particles. However, at least some of the precipitated particles conventionally obtained may be undesirably large, especially for applications calling for the acetylenic agent to be formulated into an ink for printing or marking on a label or other substrate. Accordingly, it is a common practice in the art to grind, pulverize, mill or otherwise mechanically comminute the raw acetylenic agent crystals to obtain a particulate product having desired size characteristics, for example characteristics rendering the acetylenic agent particles suitable for use in a free-flowing ink that may be effectively applied to a printed label, tag, product wrapper component or the like.
One drawback of mechanical comminution is that it adds a relatively costly step or steps to the overall process. Furthermore, the mechanical action adds heat to the sample and may cause unwanted color development. Another drawback is that the quality of the inks produced may be inconsistent or sometimes unsatisfactory. It would therefore be desirable to provide a method of preparing particulate condition-indicating acetylenic agents which yields acetylenic agents in particulate or crystallized form that are well suited for use in TTI inks, and which avoids mechanical comminution.
Furthermore, to reduce inconsistencies in the printing of TTI indicators, pursuant to the invention it is now understood that it would be desirable to limit the presence of oversized particles in the particulate acetylenic agents.
In an unrelated art, I. H. Leubner, in a research paper regarding laboratory experimentation published in J. Crystal Growth, 84: 496 (1987), 'Crystal Formation (Nucleation) in the Presence of Growth Restrainers reports that when certain compounds are present during nucleation in silver halide precipitation, more and thus smaller crystals are obtained than in their absence (abstract). Specifically, Leubner added silver nitrate and halide solutions simultaneously to a stirred 4% gelatin solution. A mercapto-tetrazole restrainer, namely 2-(3-acetamidophenyl)mercapto-tetrazole, at concentrations of from 0-(500 mg/l (0–0.05% by weight), was added to the gelatin solution (Table 1). Reported precipitating silver halide crystal sizes were progressively reduced at different concentrations from about 0.4 micron without restrainer to about 0.14 micron with 500 mg/l restrainer. A number of theoretical considerations are described to explain the results, and a mathematical model of the restrainer effect is described. The model is contemplated by Leubner as being generally applicable to describe the growth effects of restrainers on crystals. However, nothing in Leubner's data, limited as it is to the specialist photographic-related field of silver-halide-in-gelatin precipitation, provides a commercially convincing suggestion that Leubner's tetraazole restrainer would be effective to control particle size in other systems. Thus, the TTI acetylenic agents employed in the practice of the present invention are not at all like Leubner's silver halide. Furthermore, the acetylenic agent crystallization processes to which the present invention relates, which are frequently recrystallizations, are quite different from Leubner's process of in situ synthesis and precipitation of silver halide into a gelatin-rich, viscous medium. Leubner's academic theories do not appear germane to the practical commercial problems addressed by the present invention.
Accordingly, there is a need for a non-comminutive process for favorably influencing particle size in acetylenic agent crystallization processes.
The foregoing description of background art may include insights, discoveries, understandings or disclosures, or associations together of disclosures, that were not known to the relevant art prior to the present invention but which were provided by the invention. Some such contributions of the invention may have been specifically pointed out herein, whereas other such contributions of the invention will be apparent from their context. Merely because a document may have been cited here, no admission is made that the field of the document, which may be quite different from that of the invention, is analogous to the field or fields of the present invention.